The Human Immunodeficiency virus (HIV) is the causative agent of the Acquired Immunodeficiency Syndrome (AIDS). Like all retroviruses the genome of the virus encodes the Gag, Pol and Env proteins. In addition, the viral genome encodes further regulatory proteins, i.e. Tat and Rev, as well as accessory proteins, i.e. Vpr, Vpx, Vpu, Vif and Nef.
Despite public health efforts to control the spread of the AIDS epidemic, the number of new infections is still increasing. The World Health Organization estimated the global epidemic at 36.1 million infected individuals at the end of the year 2000, 50% higher than what was predicted on the basis of the data a decade ago (WHO & UNAIDS. UNAIDS, 2000). Globally, the number of new HIV-1 infections in 2000 is estimated at 5.3 million.
New therapies for fighting HIV infection and AIDS are needed. Disclosed are compositions with higher binding affinity and specificity to viral RNA, such as HIV RNA, such as TAR RNA, by conjugation to other small molecules. One example is the neomycin—Hoechst 33258 conjugates, and derivatives, as high affinity small molecule inhibitors of the Tat/TAR interaction. Conjugation of the aminoglycoside (neomycin) and Hoechst 33258 (benzimidazole) with an alkyl linker can provide a high affinity binding ligand, capable of binding to TAR with IC50 in nanomolar concentrations. The disclosed TAR binding ligands, with improved affinity and specificity over currently known molecules can aid in the fight against HIV. Quick and efficient synthesis of the disclosed compositions can be done. (Arya and Coffee 2000; Arya, Coffee et al. 2001; Arya, Coffee et al. 2001; Arya, Micovic et al. 2003; Arya and Willis 2003; Arya, Xue et al. 2003; Arya, Xue et al. 2003; Arya, Coffee et al. 2004; Arya 2005; Willis and Arya 2006; Willis and Arya 2006).